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Literature summary for 1.7.1.7 extracted from
- Novel characteristics of Trypanosoma brucei guanosine 5-monophosphate reductase distinct from host animals (2016), PLoS Negl. Trop. Dis., 10, e0004339 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene Tb927.5.2080, recombinant expression of GST-tagged enzyme in Escherichia coli strain BL21 (DE3) | Trypanosoma brucei brucei |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| mizoribine 5'-monophosphate | MZP, moderate inhibition; MZP, moderate inhibition | Homo sapiens |  |
| mizoribine 5'-monophosphate | MZP | Trypanosoma brucei brucei | |
| additional information | no inhibition by ribavirin 5'-monophosphate; no inhibition by ribavirin 5'-monophosphate | Homo sapiens | |
| additional information | ribavirin acts as an anti-trypanosomal drug in vitro with IC50 = 0.0254 mM | Trypanosoma brucei brucei | |
| NH4Cl | - |
Homo sapiens | |
| ribavirin 5'-monophosphate | RMP, competitive inhibition | Trypanosoma brucei brucei | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | Michaelis-Menten steady-state kinetics | Homo sapiens | |
| additional information | - |
additional information | Michaelis-Menten steady-state kinetics | Trypanosoma brucei brucei | |
| 0.0123 | - |
NADPH | pH 8.0, 35°C | Trypanosoma brucei brucei | |
| 0.0178 | - |
GMP | pH 8.0, 35°C | Homo sapiens | |
| 0.0221 | - |
GMP | pH 8.0, 35°C | Homo sapiens | |
| 0.0293 | - |
NADPH | pH 8.0, 35°C | Homo sapiens | |
| 0.0348 | - |
NADPH | pH 8.0, 35°C | Homo sapiens | |
| 0.0893 | - |
GMP | pH 8.0, 35°C | Trypanosoma brucei brucei | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| glycosome | of Trypanosoma brucei bloodstream forms | Trypanosoma brucei brucei | 20015 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| KCl | highly activating, best monovalent cation, amino acid sequences of putative K+-binding sites of TbGMPR, overview | Trypanosoma brucei brucei | |
| additional information | the human enzyme is not activated in the presence of KCl instead of NaCl | Homo sapiens | |
| NaCl | activating | Homo sapiens | |
| NaCl | activating | Trypanosoma brucei brucei | |
| NH4Cl | highly activating | Trypanosoma brucei brucei | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| GMP + NADPH + H+ | Homo sapiens | - |
IMP + NH3 + NADP+ | - |
? | |
| GMP + NADPH + H+ | Trypanosoma brucei brucei | - |
IMP + NH3 + NADP+ | - |
? | |
| GMP + NADPH + H+ | Trypanosoma brucei brucei 927/4 GUTat10.1 | - |
IMP + NH3 + NADP+ | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P36959 | - |
- |
| Homo sapiens | Q9P2T1 | - |
- |
| Trypanosoma brucei brucei | Q57ZS7 | cf. EC 1.1.1.205 | - |
| Trypanosoma brucei brucei 927/4 GUTat10.1 | Q57ZS7 | cf. EC 1.1.1.205 | - |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant GST-tagged enzyme from Escherichia coli strain BL21 (DE3) by glutathione affinity chromatography, the tag is cleaved off by a commercial protease, followed by dialysis | Trypanosoma brucei brucei |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| bloodstream form | - |
Trypanosoma brucei brucei | - |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| 21.7 | - |
pH 8.0, 35°C, with NaCl | Trypanosoma brucei brucei |
| 30.6 | - |
pH 8.0, 35°C, with NH4Cl | Trypanosoma brucei brucei |
| 43.8 | - |
pH 8.0, 35°C, with KCl | Trypanosoma brucei brucei |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| GMP + NADPH + H+ | - |
Homo sapiens | IMP + NH3 + NADP+ | - |
? | |
| GMP + NADPH + H+ | - |
Trypanosoma brucei brucei | IMP + NH3 + NADP+ | - |
? | |
| GMP + NADPH + H+ | - |
Trypanosoma brucei brucei 927/4 GUTat10.1 | IMP + NH3 + NADP+ | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| GMPR | - |
Homo sapiens |
| GMPR | - |
Trypanosoma brucei brucei |
| HsGMPR1 | - |
Homo sapiens |
| HsGMPR2 | - |
Homo sapiens |
| Tb927.5.2080 | - |
Trypanosoma brucei brucei |
| TbGMPR | - |
Trypanosoma brucei brucei |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 35 | 37 | assay at | Homo sapiens |
| 38 | - |
- |
Trypanosoma brucei brucei |
Temperature Range [°C]
| Temperature Minimum [°C] | Temperature Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 15 | 50 | activity range, profile overview | Trypanosoma brucei brucei |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.265 | - |
GMP | pH 8.0, 35°C | Homo sapiens | |
| 0.284 | - |
GMP | pH 8.0, 35°C | Homo sapiens | |
| 0.519 | - |
GMP | pH 8.0, 35°C | Trypanosoma brucei brucei | |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 6.5 | - |
- |
Trypanosoma brucei brucei |
| 8 | - |
assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NADPH | - |
Homo sapiens | |
| NADPH | - |
Trypanosoma brucei brucei | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | inhibition kinetics | Trypanosoma brucei brucei | |
| 0.00446 | - |
ribavirin 5'-monophosphate | pH 8.0, 35°C | Trypanosoma brucei brucei | |
pI Value
| Organism | Comment | pI Value Maximum | pI Value |
|---|---|---|---|
| Trypanosoma brucei brucei | sequence calculation | - |
9.7 |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.0237 | - |
pH 8.0, 35°C | Trypanosoma brucei brucei | mizoribine 5'-monophosphate | |
| 0.0693 | - |
pH 8.0, 35°C | Homo sapiens | mizoribine 5'-monophosphate | |
| 0.1018 | - |
pH 8.0, 35°C | Trypanosoma brucei brucei | ribavirin 5'-monophosphate | |
| 0.1191 | - |
pH 8.0, 35°C | Homo sapiens | mizoribine 5'-monophosphate | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | GMPR shows high similarities in amino acid sequence and structure to inosine 5'-monophosphate dehydrogenase (IMPDH), EC 1.1.1.205, the enzyme catalyzing the NAD+-dependent oxidation of IMP to xanthosine 5'-monophosphate (XMP). But GMPR and IMPDH are generally distinguished by the cystathionine beta-synthase (CBS) domain, which is well conserved in IMPDHs but absent in GMPRs | Homo sapiens |
| evolution | GMPR shows high similarities in amino acid sequence and structure to inosine 5'-monophosphate dehydrogenase (IMPDH), EC 1.1.1.205, the enzyme catalyzing the NAD+-dependent oxidation of IMP to xanthosine 5'-monophosphate (XMP). But GMPR and IMPDH are generally distinguished by the cystathionine beta-synthase (CBS) domain, which is well conserved in IMPDHs but absent in GMPRs | Trypanosoma brucei brucei |
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